Fungal polyketide synthase

Fungal Polyketide Synthases Fungal NR-PKS Fungal PR-PKS Fungal HR-PKS Conclusion... 

Recently, bacterial NRPS modules with the organization of A-KR-PCP have been discovered in the valino-mycin and cereulide synthetases. The A domains of these modules selectively activate a-keto acids. After the resulting adenylate is transferred to the PCP domain, the a-ketoacyl- -PCP intermediate is reduced to a PCP-bound, a-hydroxythioester by the KR domain. These domains use NAD(P)H as a cofactor and are inserted into A domains between two conserved core motifs analogous to MT domains. Their substrate specificity differs from that of polyketide synthase KR domains, which reduce /3-ketoacyl substrates. Similar fungal NRPSs, such as beauvericin synthetase, utilize A domains that selectively activate a-hydroxy acids. These molecules are thought to be obtained using an in trans KR domain, which directly reduces the necessary, soluble a-keto acid. 

Bingle, L. E. H., Simpson, T. J., and Lazarus, C. M. (1999). Ketosynthase domain probes identify two subclasses of fungal polyketide synthase genes. Fungal Genet. Biol. 26, 209-223. 

DJ Bedford, E Schweizer, DA Hopwood, C Khosla. Expression of a functional fungal polyketide synthase in the bacterium Streptomyces coelicolor A3(2). J Bacteriol... 

Hutchinson, C.R., Kennedy, J., Park, C., Kendrew, S., Auclair, K., and Vederas, J. (2000). Aspects of the biosynthesis of non-aromatic fungal polyketides by iterative polyketide synthases. Antonie Van Leeuwenhoek 78 287-295. 

Fig. 2a-d. The major architectural paridigms of fatty acid and polyketide synthases. Relationships between genes encoding a bacterial aromatic polyketide synthases, b eukaryotic fatty acid synthases and fungal polyketide synthases, c modular polyketide synthases, and d plant polyketide synthases... 

Figure 1 Generic polyketide assembly pathway reactions catalyzed by iterative fungal polyketide synthases. The assembly sequence for the squalesatin tetraketide intermediate 37 is shown for illustration.

Fuji I, Watanabe A, Sankawa U, Ebizuka Y. Identification of a claisen cyclase domain in fungal polyketide synthase WA, a naphthpyrone synthase of Aspergillus nidulans. Chem. Biol. 2001 8 189-197. 

Cox RJ, Glod F, Hurley D, Lazarus CM, Nicholson TP, Rudd BAM, Simpson TJ, Wilkinson B, Zhang Y. Rapid cloning and expression of a fungal polyketide synthase gene involved in squalestatin biosynthesis. Chem. Commun. 2004 2260-2261. 

If identical plant and microbial polyketides are indeed derived by common or closely related pathvwiys, it would appear that higher plant species can produce both types of synthases required for the formation of mode F and mode S-cyclised fused ring polyketides. The biosynthesis of aloesaponarin II by steptomycetes is known to involve an iterative type IIPKS and, by analogy with other fungal aromatic polyketide synthases, it is likely that a type I PKS is responsible for the formation of chrysophanol. However, at present little is known of the nature of PKSs responsible for the formation of fused ring polyketides in plants. 

Intriguingly LNKS, one of the best investigated fungal polyketide synthases has long been known to possess NRPS domains (2). Similarly to FUSS and TENS, it contains a seemingly intact condensation domain after the PKS ACP, and the TV-terminal region of the adenylation (A) domain. However the catalytic... 

Determination of chain iength by fungal polyketide synthases... 

Yang G, Rose MS, Turgeon BG, Yoder OC. A polyketide synthase is required for fungal virulence and production of the polyketide T-toxin. Plant Cell 8 2139-2150, 1996. 

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